Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rua Evaristo da Veiga 83/509, Rio de Janeiro, RJ, Brazil.
Arq Bras Cardiol. 2011 Mar;96(3):172-8. doi: 10.1590/s0066-782x2011005000015. Epub 2011 Feb 4.
The long QT syndrome (LQTS) is an inherited arrhythmia syndrome with increased QT interval and risk of sudden death. Mutations in genes KCNQ1, KCNH2 and SCN5A account for 90% of cases with genotype determined, and genotyping is informative for genetic counseling and better disease management.
Molecular investigation and computational analysis of gene variants of KCNQ1, KCNH2 and SCN5A associated with LQTS, in families with the disease.
The coding regions of genes KCNQ1, KCNH2 and SCN5A in patients with LQTS and their family members were sequenced and analyzed using Geneious ProTM software.
Two families with clinical criteria for LQTS were investigated. The proband of Family A had QTC = 562 ms, Schwartz Score = 5.5. The genotyping identified the G1714A mutation in the KCNH2 gene. QTC = 521 ± 42 ms was observed in family members carrying the mutation against QTC = 391 ± 21 ms for non-carriers. The proband of Family B had QTc = 551 ms, Schwartz Score = 5.5. The genotyping identified the G1600T mutation, in the same gene. The analysis of family members revealed QTC = 497 ± 42 ms in mutation carriers, compared with QTC = 404 ± 29 ms in non-carriers.
Two gene variants previously associated with LQTS were found in two families clinically diagnosed with LQTS. The prolongation of the QT interval was observed in all family members carrying the mutations. A strategy was developed to identify variants of genes KCNQ1, KCNH2 and SCN5A, making it possible to train technical staff for future application to diagnosis routine.
长 QT 综合征（LQTS）是一种遗传性心律失常综合征，伴有 QT 间期延长和猝死风险。KCNQ1、KCNH2 和 SCN5A 基因突变占 90%的病例，基因型确定，基因分型对遗传咨询和更好的疾病管理具有信息性。
对伴有 LQTS 的患者及其家庭成员的 KCNQ1、KCNH2 和 SCN5A 基因变异进行分子研究和计算分析。
使用 Geneious ProTM 软件对 LQTS 患者及其家族成员的 KCNQ1、KCNH2 和 SCN5A 基因的编码区进行测序和分析。
研究了 2 个具有 LQTS 临床标准的家族。家族 A 的先证者 QTC = 562 ms，Schwartz 评分 = 5.5。基因分型确定 KCNH2 基因的 G1714A 突变。携带突变的家族成员 QTC = 521 ± 42 ms，而非携带者 QTC = 391 ± 21 ms。家族 B 的先证者 QTc = 551 ms，Schwartz 评分 = 5.5。基因分型确定了同一基因中的 G1600T 突变。对家族成员的分析显示，突变携带者的 QTC = 497 ± 42 ms，而非携带者的 QTC = 404 ± 29 ms。
在临床上诊断为 LQTS 的 2 个家族中发现了与 LQTS 相关的 2 个基因变异。所有携带突变的家族成员的 QT 间期均延长。开发了一种鉴定 KCNQ1、KCNH2 和 SCN5A 基因变异的策略，使未来能够培训技术人员进行常规诊断应用。
